TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27543	82852;82853;82854	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
N2AB	25902	77929;77930;77931	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
N2A	24975	75148;75149;75150	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
N2B	18478	55657;55658;55659	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
Novex-1	18603	56032;56033;56034	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
Novex-2	18670	56233;56234;56235	chr2:178563505;178563504;178563503	chr2:179428232;179428231;179428230
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-88
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1459
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/T	None	None	0.722	N	0.514	0.349	0.384752662912	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.877	likely_pathogenic	0.8922	pathogenic	-1.771	Destabilizing	0.633	D	0.538	neutral	None	None	None	None	N
R/C	0.3582	ambiguous	0.3187	benign	-1.726	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
R/D	0.9909	likely_pathogenic	0.9918	pathogenic	-0.854	Destabilizing	0.923	D	0.586	neutral	None	None	None	None	N
R/E	0.869	likely_pathogenic	0.879	pathogenic	-0.635	Destabilizing	0.633	D	0.538	neutral	None	None	None	None	N
R/F	0.9244	likely_pathogenic	0.924	pathogenic	-0.945	Destabilizing	0.987	D	0.747	deleterious	None	None	None	None	N
R/G	0.8895	likely_pathogenic	0.9065	pathogenic	-2.125	Highly Destabilizing	0.722	D	0.551	neutral	D	0.559909185	None	None	N
R/H	0.2105	likely_benign	0.1873	benign	-1.946	Destabilizing	0.961	D	0.557	neutral	None	None	None	None	N
R/I	0.7922	likely_pathogenic	0.7785	pathogenic	-0.749	Destabilizing	0.949	D	0.731	prob.delet.	D	0.523700675	None	None	N
R/K	0.2554	likely_benign	0.2669	benign	-1.215	Destabilizing	0.003	N	0.263	neutral	N	0.489805889	None	None	N
R/L	0.6491	likely_pathogenic	0.6744	pathogenic	-0.749	Destabilizing	0.775	D	0.551	neutral	None	None	None	None	N
R/M	0.7673	likely_pathogenic	0.7589	pathogenic	-1.303	Destabilizing	0.996	D	0.624	neutral	None	None	None	None	N
R/N	0.9665	likely_pathogenic	0.9653	pathogenic	-1.227	Destabilizing	0.923	D	0.503	neutral	None	None	None	None	N
R/P	0.9959	likely_pathogenic	0.9976	pathogenic	-1.078	Destabilizing	0.961	D	0.675	neutral	None	None	None	None	N
R/Q	0.2224	likely_benign	0.2276	benign	-1.067	Destabilizing	0.858	D	0.531	neutral	None	None	None	None	N
R/S	0.9166	likely_pathogenic	0.9216	pathogenic	-2.077	Highly Destabilizing	0.565	D	0.517	neutral	N	0.520405312	None	None	N
R/T	0.8395	likely_pathogenic	0.8262	pathogenic	-1.647	Destabilizing	0.722	D	0.514	neutral	N	0.503719862	None	None	N
R/V	0.8151	likely_pathogenic	0.8157	pathogenic	-1.078	Destabilizing	0.923	D	0.682	prob.neutral	None	None	None	None	N
R/W	0.5199	ambiguous	0.5179	ambiguous	-0.491	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
R/Y	0.8603	likely_pathogenic	0.8397	pathogenic	-0.333	Destabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.